Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2

Abstract

Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti-SARS-CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (n 5 113) and 3 mo (n 5 79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 Ags, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never-before-assessed COVID-19 symptoms, that consistently correlate with high anti-SARS-CoV-2 Ab levels. We detected anti-SARS-CoV-2 Abs in 98% of COVID-19 convalescent subjects 5 wk after symptom resolution, and Ab levels did not decline at 3 mo. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 Ab levels. Moreover, we report for the first time (to our knowledge) that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti-SARS-CoV-2 Ab levels. Our results provide robust and new insights into the development and persistence of anti-SARS-CoV-2 Abs. ImmunoHorizons, 2021, 5: 466-476.

Anti-membrane and anti-spike antibodies are long-lasting and together discriminate between past COVID-19 infection and vaccination

“…This ELISA was not as strong as the anti-RBD assay, given the AUC of 0.919 (Wald 95% CI 0.879, 0.959), sensitivity of 91%, and specificity of 88% (Figure 1D). The lower accuracy of this test is consistent with previous reports with different anti-nucleocapsid tests and may be due to inconsistent immune responses to SARS-CoV-2 nucleocapsid in COVID-19 convalescent subjects and cross-reactivity with the nucleocapsid of common cold coronaviruses 3,6,7,14,15 . Nonetheless, as expected, there was no difference in anti-nucleocapsid IgG levels between naïve versus vaccinated subjects or between 12 month COVID-19 convalescent vaccinated versus unvaccinated subjects (Figure 1E).…”

“…Demographic and clinical information were collected by questionnaire and abstraction of the electronic medical record. COVID-19 severity was diverse with mild (n=12), moderate (n=86), severe (n=15) and critical (n=8) clinical phenotypes represented as previously defined 14 . Subjects provided blood and clinical information 5 weeks (n=121), 3 months (n=115), 6 months (n=98) and 12 months (n=100) after symptom resolution.…”

“…Sera and data collected prior to 2019 from COVID-19 naïve adults without inflammatory disease (except one subject with psoriatic arthritis using adalimumab to match two COVID-19 convalescent subjects using adalimumab) were obtained from the University of Wisconsin (UW) Rheumatology Biorepository, described in 20 . COVID-19 convalescent human sera and data were obtained from the UW COVID-19 Convalescent Biorepository, as described in 14 . Briefly, in the spring of 2020, adults who tested positive by PCR for SARS-CoV-2 at UW Health were invited to participate in the COVID-19 Convalescent Biorepository until 121 subjects were recruited.…”

Persistence of Naturally Acquired and Functional SARS-CoV-2 Antibodies in Blood Donors One Year after Infection

“…This is in contrast to the study conducted by Lynch et al who demonstrated that SARS-CoV-2 antibody responses were significantly higher in patients with a severe compared to a milder disease course [ 50 ]. Another study showed that as well as severity of disease course, specific COVID-19 symptoms, namely fever, body aches and low appetite, might go along with a higher antibody response [ 51 ]. However, a direct comparison of those studies with our data is difficult as participant cohorts differed substantially with regard to symptoms and disease course.…”

Associations Between Symptoms, Donor Characteristics and IgG Antibody Response in 2082 COVID-19 Convalescent Plasma Donors

“…In general, SARS-CoV-2 antibody levels are higher in patients with a severe disease outcome ( 14 ). A recent study in which COVID-19 convalescent plasma (CCP) donors were followed for three months after symptom resolution showed that greater disease severity, older age, male sex, and high BMI correlate with high SARS-CoV-2 antibody levels ( 7 , 15 ). The same study also reported that particularly the symptoms fever, body aches, and low appetite correlate with high SARS-CoV-2 antibody levels.…”